The purpose of Core A is to provide common facilities and expertise for the immunopathological studies in all four projects of the Program Project. One might question the need for pathological analysis in a Program Project whose principal goal is the establishment of transplantation tolerance, since, if this goal were achieved, there would be little, if any graft pathology to analyze. However, it is clear that guidance from pathological analysis is essential to achieve our goal. The primary role of the pathological analyses in these tolerance protocols is to document and characterize: 1) The status of the graft (nature of infiltrate, presence of acute or chronic rejection, including humoral component) 2) The status of chimerism (cell type, distribution) 3) The systemic effects of the protocols (toxicity, complications). In addition, many valuable opportunities arise in the course of the proposed studies that will give insights into the mechanisms of graft rejection and acceptance. In particular, with protocol biopsies in the large animal studies we have the opportunity to: 4) Distinguish the nature of the infiltrate that leads to acceptance vs. rejection 5) Analyze grafts for precursor lesions that predict outcome, e.g., chronic rejection. The pathology features will be assessed and graded by the same group pathologists for all studies, which we consider an important asset of the Program Project. The panel of antibodies and cytokine probes will also be comparable, whenever possible. This should promote cross-fertilization among the projects by extension of novel findings and provide insights into the general significance of the results in one project by comparing and contrasting grafts in different species and between different organs. We also have a well annotated tissue bank of frozen and paraffin embedded tissue available from our previous transplantation experiments (>5000 samples), which can be drawn upon to expand and refine our analysis.